Red Cell Alloimmunization in Pregnancy Case Presentation Michael McNamara, DO, FACOG Sanford Maternal Fetal Medicine

Allo-Immunization in Pregnancy Objectives Understand the problem of red cell alloimmunization during pregnancy Diagnosis of red cell alloimmunization Surveillance and treatment of patient with red cell alloimmunization

Disclaimer No conflicts to disclose

Red Cell Alloimmunization Maternal immune system makes antibodies against fetal red cell antigen (paternal origin) Common etiology for immune hydrops Incidence 6.7/1000 (2002 data) Most commonly due to Rh disease, D antigen

Etiology Mom exposed to foreign red cell antigen Fetal blood (paternal origin) Blood transfusion (most often Kell) Mom develops antibodies Antibodies IgG or IgM IgG small enough to pass through placenta Attacks (destroys) fetal red blood cells Fetal anemia, subsequent hydrops

Anemia Results in release of erythroblasts into fetal circulation Increased cardiac output Tissue hypoxia Hydrops (fluid in two or more fetal compartments) Ascites Skin edema Pleural effusions Pericardial effusions Polyhydramnios Seen when fetal hemoglobin 7-10 g/dL below normal

Hydrops

Rh Alloimmunization D antigen on short arm of chromosome 1 Absence (Rh-) homozygous 15% Caucasian European 30% Spanish from Basque region of Spain 8% African American, Hispanic (Mexican, South American) < 1% native American, Eskimo, Chinese, Japanese

Rh and Rhogam Prevention of Alloimmunization Blood type incompatability Passive immunization 300 ug protects against 30 ml fetal blood Given 28 weeks and following delivery (if fetus Rh +) Quantify amount (Rhogam) based on testing of amount of fetal blood in maternal blood

Kleihauer-Betke Test

Evaluation of Red Cell Alloimmunization Maternal antibody titers Fetus Ultrasound

Antibody Titers Degree that Mom is responding to fetal antigen Critical titer – titer with significant risk for fetal hydrops Usually between 1:8 and 1:32 for D antibodies Use same for other red cell antibodies except Kell

Fetal Evaluation Paternal testing Chorionic villus sampling Amniocentesis Cell free DNA Fetal blood typing

Ultrasound Hydrops – abnormal fluid in two or more compartments Pleural effusion, pericardial effusion, ascites, skin edema, polyhydramnios Doppler studies Middle cerebral artery (MCA)doppler studies

Fetal Surveillance Titers checked monthly to 24 weeks, then every two weeks for critical titer Once critical titer is reached (titers checked monthly until 24 weeks and then every 2 weeks) further evaluation needed Amniocentesis Umbilical vein sampling Ultrasound

Surveillance Amniocentesis (serial) Cord Sampling Monitor bilirubin in amniotic fluid Amount (OD 450) vs gestational age Plot on Liley graph (curve) to see if fetus anemic Cord Sampling 1-2% of fetal loss 50% chance for increasing hemolytic response

Liley Curve

Surveillance Ultrasound Middle cerebral artery Doppler blood flow (MCA) Anemia increases blood flow (velocity), less cells Plot the peak systolic velocity against gestational age 1.5 multiples of the median (MoM) or greater suspect for fetal anemia, needing fetal blood sampling, transfusion

MCA Peak Systolic Velocity

MCA Doppler

MCA Dopplers Non invasive Sensitivity 88% Negative predictive value of 89%

Management Identify titer-1st episode usually no consequence for fetus Paternal status / fetal status Titers monthly until 24 weeks, every two weeks thereafter Critical titer – MCA Dopplers every 1-2 weeks Abnormal MCA – fetal umbilical vein sampling, transfusion

Next Pregnancy High risk if previous pregnancy Fetal loss due to hydrops Fetal transfusion Neonatal exchange transfusion

Case 34 year old Gravid 2, para 1 Presented in consult at 19+ weeks D antibody titer of 1:64 Previous cesarean x 1 Drug use history, currently on suboxone

Fetus Fetus with D antigen? Father not available for screening Normal anatomy except echogenic focus in heart (soft marker for trisomy 21) Normal MCA Doppler Mom desired amniocentesis for karyotype and assess fetal Rh status

Patient Normal karyotype Fetal + D antigen Normal MCA doppler

Graph for MCA Doppler

Patient 33+5 weeks Ultrasound showing elevated MCA peak systolic velocity Doppler at 2.0 MoM Fetal ascites, polyhydramnios of 30.5 cm

Fetal weight graph

Gestational Age, MCA Dopplers Doppler (MoM) 20+5 < 1.0 23+5 1.1 25+2 28+5 1.13 30+5 1.11 32+5 1.24 33+5 2.0

Patient Admitted, antenatal steroids Delivery at 33+6 weeks repeat cesarean Earlier in pregnancy, consideration for umbilical vein sampling and RBC transfusion Uneventful post operative course